CD63 Associates with the αIIbβ3 Integrin-CD9 Complex on the Surface of Activated Platelets

Sara J. Israels; Eileen M. McMillan-Ward; Jeffrey Easton; Catherine Robertson; Archibald McNicol

doi:10.1055/s-0037-1612916

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(01): 134-141
DOI: 10.1055/s-0037-1612916

Review Article

Schattauer GmbH

CD63 Associates with the α_IIbβ₃ Integrin-CD9 Complex on the Surface of Activated Platelets

Sara J. Israels

¹Departments of Pediatrics and Oral Biology and the Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada

,

Eileen M. McMillan-Ward

¹Departments of Pediatrics and Oral Biology and the Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada

,

Jeffrey Easton

¹Departments of Pediatrics and Oral Biology and the Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada

,

Catherine Robertson

¹Departments of Pediatrics and Oral Biology and the Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada

,

Archibald McNicol

¹Departments of Pediatrics and Oral Biology and the Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada

› Author Affiliations

Abstract

Summary

The tetraspanins are integral membrane proteins expressed on cell surface and granular membranes of hematopoietic cells and have been identified in multi-molecular complexes with specific integrins. In resting platelets, CD63, a member of the tetraspanin superfamily, is present in dense granule and lysosomal membranes and, following platelet activation, translocates to the plasma membrane. In the present study, platelet activation by thrombin leads to incorporation of CD63 into the Triton-insoluble actin cytoskeletal fraction. This incorporation was inhibited by preincubation of platelets with RGDS or EGTA and did not occur in platelets from a patient with Glanzmann’s thrombasthenia, suggesting that it was dependent upon α_IIbβ₃. In activated platelets, the anti-CD63 MoAb, D545, co-immunoprecipitated CD63 with other surface-labeled proteins, including α_IIbβ₃ and another tetraspanin, CD9. The association of CD63 with CD9 and α_IIbβ₃ was not inhibited by preincubation of platelets with RGDS or EGtA. D545 did not inhibit the adhesion of activated platelets to purified extracellular matrix proteins, but significantly decreased adhesion of thrombin-activated platelets to neutrophils in a rosetting assay. D545 also caused disaggregation of platelets stimulated by ADP, but had no effect on aggregation induced by other agonists. These results are consistent with the proposal that CD63 becomes part of an α_IIbβ₃-CD9-CD63 integrintetraspanin complex in activated platelets – an association that may modulate the function of α_IIbβ₃-dependent interaction with other cells such as neutrophils.

Keywords

CD antigens - blood platelets - platelet glycoprotein IIb/IIIa complex - platelet activation - cell membrane

Full Text

References

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